Felbinac, which is a non-steroidal anti-inflammatory analgesic, is an active metabolite of fenbufen and a drug having high anti-inflammatory and analgesic activity. Felbinac has been transdermally administered to avoid systemic side effects and available as external preparations such as a gel, a liquid, a cataplasm, and a plaster.
Felbinac itself has very low solubility in various solvents. Thus, a variety of solubilizers have been conventionally used in such external preparations to enhance the transdermal absorption of felbinac.
For example, Patent Document 1 has proposed a felbinac-containing plaster which contains crotamiton having high solubilizing ability for felbinac as an essential component. Also, Patent Document 2 has proposed a plaster in which N-methyl-2-pyrrolidone and polyethylene glycol are formulated as the solubilizers. Many of such solubilizers, however, have caused irritation to the skin. Moreover, when such liquid components are formulated in an adhesive patch, a change of the physical properties of the adhesive patch may be caused over time by the bleed-out to the surface (the exudation to the surface) of the adhesive patch.
In addition, Patent Document 3 has proposed a plaster free of crotamiton and containing a styrene-isoprene-styrene block copolymer, a rosin resin, a plasticizer, 1-menthol, and felbinac. This plaster is an adhesive patch in which felbinac is uniformly dispersed in a semi-molten state in the adhesive layer, i.e., in a state wherein felbinac is present in a molten state and in a fine crystalline state simultaneously. The drug permeability however was not sufficient because part of felbinac was present in a crystalline state.
Further, a combination preparation in which a non-steroidal anti-inflammatory analgesic and a local anesthetic are formulated has been studied wherein the preparation has both an anti-inflammatory activity of the non-steroidal anti-inflammatory analgesic and an analgesic activity of the local anesthetic.
For example, Patent Document 4 and Patent Document 5 have proposed a cataplasm in which a non-steroidal anti-inflammatory analgesic such as indomethacin, felbinac, diclofenac sodium and loxoprofen sodium and a local anesthetic such as lidocaine, benzocaine and dibucaine are formulated. Also, Patent Document 6 and Patent Document 7 have proposed a tape in which a non-steroidal anti-inflammatory analgesic and a local anesthetic are formulated respectively.
In general, however, many local anesthetics are basic drugs, while many non-steroidal anti-inflammatory analgesics to be formulated together are acidic drugs including indomethacin and ketoprofen. Accordingly, when these both drugs were simultaneously formulated in the adhesive patch, these formed salts and inhibited the drug releasing of each other, thereby failing to obtain a desired medicinal effect.